Pathology of Tuberculosis, pathogenesis of Tuberculosis

Pathology of Tuberculosis, pathogenesis of Tuberculosis

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  TUBERCULOSIS MITHUN VENUGOPAL DEPT.OF PATHOLOGY
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  INTRODUCTION • Tuberculosis isa chronic granulomatous communicable disease in which the lungs are the prime target, although any other organ may be infected. • Mycobacterium tuberculosis causes tuberculosis in the lungs and other tissues of the human body. The organism is a strict aerobe and thrives best in tissues with high oxygen tension such as in the apex of the lung. • Out of various pathogenic strains for human disease included in Mycobacterium tuberculosis complex, currently most common is M. tuberculosis hominis (human strain), while M. tuberculosis bovis (bovine strain) is a common pathogen to human who consume unpasteurised milk. • Other less common strains included in the complex are M. africanum (isolated from patients from parts of Africa), M. microti, M. pinnipedii and M. canettii.
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  MODE OF TRANSMISSION •Inhalation of organisms present in fresh cough droplets or in dried sputum from an open case of pulmonary tuberculosis. • Ingestion of the organisms leads to development of tonsillar or intestinal tuberculosis. This mode of infection of human tubercle bacilli is from self-swallowing of infected sputum of an open case of pulmonary tuberculosis, or ingestion of bovine tubercle bacilli from milk of diseased cows. • Inoculation of the organisms into the skin may rarely occur from infected postmortem tissue. • Transplacental route results in development of congenital tuberculosis in foetus from infected mother and is a rare mode of transmission.
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  SPREAD OF TUBERCULOSIS •Local spread: This takes place by macrophages carrying the bacilli into the surrounding tissues. • Lymphatic spread: Tuberculosis is primarily an infection of lymphoid tissues. The bacilli may pass into lymphoid follicles of pharynx, bronchi, intestines or regional lymph nodes resulting in regional tuberculous lymphadenitis. • Haematogenous spread: This occurs either as a result of tuberculous bacillaemia because of the drainage of lymphatics into the venous system or due to caseous material escaping through ulcerated wall of a vein. This produces millet seed-sized lesions in different organs of the body like lungs, liver, kidneys, bones and other tissues and is known as miliary tuberculosis. • By the natural passages: infection may spread from lung lesions into pleura, transbronchial spread into the adjacent lung segments, into peritoneal cavity (tuberculous peritonitis), infected sputum into larynx (tuberculous laryngitis), swallowing of infected sputum (ileo-caecal tuberculosis), and renal lesions into ureter and down to trigone of bladder.
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  PATHOGENESIS • Entry intomacrophages and phagocytosis • Replication in macrophages: Tuberculosis bacilli inhibits the maturation of phagosome and blocks the formation of phagolysosome, allowing the bacilli to replicate and protected from the microcidal mechanism of lysosome. • Increased recruitment of macrophages from blood monocytes. • As a part of body’s immune response, T and B cells are activated. Activated CD4+T cells develop the cell-mediated delayed type hypersensitivity reaction, while B cells result in formation of antibodies which play no role in body’s defence against tubercle bacilli.
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  PATHOGENESIS • In 2-3days, the macrophages undergo structural changes as a result of immune mechanisms. These modified macrophages resemble epithelial cells and are called epithelioid cells. • Some of the macrophages form multinucleated giant cells by fusion of adjacent cells. • Around the mass of epithelioid cells and giant cells is a zone of lymphocytes, plasma cells and fibroblasts. The lesion at this stage is called hard tubercle due to absence of central necrosis.
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  PATHOGENESIS • Within 10-14days, the centre of the cellular mass begins to undergo caseation necrosis, characterised by cheesy appearance and high lipid content. This stage is called soft tubercle which is the hallmark of tuberculous lesions. The development of caseation necrosis is possibly due to interaction of mycobacteria with activated T cells as well as by direct toxicity of mycobacteria on macrophages. • The soft tubercle which is a fully-developed granuloma with caseous centre does not favour rapid proliferation of tubercle bacilli.
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  TYPES OF TUBERCULOSIS •Lung is the main organ affected in tuberculosis. Depending upon the type of tissue response and age, the infection with tubercle bacilli is of 2 main types: 1. PRIMARY TUBERCULOSIS 2. SECONDARY TUBERCULOSIS
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  PRIMARY TUBERCULOSIS • Theinfection of an individual who has not been previously infected or immunized is called primary tuberculosis or Ghon’s complex or childhood tuberculosis. • Primary complex or Ghon’s complex is the lesion produced in the tissue of portal of entry with foci in the draining lymphatic vessels and lymph nodes. • The most commonly involved tissues for primary complex are lungs and hilar lymph nodes.
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  • Other tissueswhich may show primary complex are tonsils and cervical lymph nodes, and in the case of ingested bacilli the lesions may be found in small intestine and mesenteric lymph nodes. • The incidence of disseminated form of progressive primary tuberculosis is particularly high in immunocompromised host e.g., in patients of AIDS. PRIMARY TUBERCULOSIS
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  Primary complex orGhon’s complex in lungs consists of 3 components: • Pulmonary component: Lesion in the lung is the primary focus or Ghon’s focus. Microscopically, the lung lesion consists of tuberculous granulomas with caseation necrosis. • Lymphatic vessel component: The lymphatics draining the lung lesion contain phagocytes containing bacilli and may develop beaded, miliary tubercles along the path of hilar lymph nodes. • Lymph node component: This consists of enlarged hilar and tracheo-bronchial lymph nodes in the area drained. PRIMARY TUBERCULOSIS
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  Fate Of PrimaryTuberculosis • Fibrosis and calcification: The lesions of primary tuberculosis of lung commonly do not progress but instead heal by fibrosis, and in time undergo calcification. • Progressive primary tuberculosis: In some cases, the primary focus in the lung continues to grow and the caseous material is disseminated through bronchi to the other parts of the same lung or the opposite lung.
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  Fate Of PrimaryTuberculosis • Primary miliary tuberculosis: At times, bacilli may enter the circulation through erosion in a blood vessel and spread to various tissues and organs. The lesions are seen in organs like the liver, spleen, kidney, brain and bone marrow. • Progressive secondary tuberculosis: In certain circumstances like in lowered resistance of the host, the healed lesions of primary tuberculosis may get reactivated. The bacilli lying dormant in acellular caseous material are activated and cause progressive secondary tuberculosis.
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  SECONDARY TUBERCULOSIS • Theinfection of an individual who has been previously infected or sensitised is called secondary, or post-primary or reinfection, or chronic tuberculosis. • The infection may be acquired from endogenous source such as reactivation of dormant primary complex; or exogenous source such as fresh dose of reinfection by the tubercle bacilli. • Secondary tuberculosis occurs most commonly in lungs in the region of apex. Other sites and tissues which can be involved are tonsils, pharynx, larynx, small intestine and skin.
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  CLINICAL FEATURES OFTUBERCULOSIS • Productive cough, may be with haemoptysis • Pleural effusion • Dyspnoea • Orthopnoea • Chest X-ray may show typical apical changes like pleural effusion, nodularity, and miliary or diffuse infiltrates in the lung parenchyma. • Systemic features such as fever, night sweats, fatigue, loss of weight and appetite.
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  LABORATORY DIAGNOSIS OFTUBERCULOSIS • Positive Mantoux skin test • Positive sputum for AFB (on smear or culture) • Complete hemogram (lymphocytosis) • Chest X-ray (characteristic hilar nodules and other parenchymal changes) • Fine needle aspiration cytology of an enlarged peripheral lymph node is quite helpful for confirmation of diagnosis.